Manufacturing substituted hydroxy-omega-amino-acetophenones



Patented Sept. 12, 1933 UNITEDnS' I'A-TES ,PA'TENT OFFICE MANUFACTURING 'sUBsTITUTEDi HY- DROXY-w-AMINO-ACETOPHENONES' Helmut Legerlotz, Berlin, Germany, assignor. to

Frederick Stearns & Company, Detroit, Mich.

V s Claims. (01. 260128.5)

This invention has reference to 'hydroxylated acetophenones and in particular toN -a1kyl-substituted, as well as to N aryl-sub-stituted so-called hydroxy-w-amino-acetophenones, and it is one of the objects of this invention to devise a method of manufacturing such products by means of which extremely high yields of such products may be obtained in a comparatively easy and not complicated manner. It is well known that according to the previous art (see 'for instance Archiv fiir Pharma'cie' 237, page 222) the reaction of halogen-compounds of the type CeHs-COCH2.X,

where X designates a halogen, with amines for theformation of bodie'sof the general type CeH5 COCI-I2 NHR where R means an alkyl oran. aryl radical results in verylunsatisfactory'low yields; and in most cases moreover, this reaction produces mixtures which can only be separated with great 'difliculty. In view of these facts some scientists. Gabriel for instance, following the indications of the Hinsberg-method have suggested to substie tute in the compounds above mentioned the halogen by the rnethyl-amino-residue and by the aid of the potassium-salt of the para-toluolsulfon-methylamine (Berichte d. Chemisch. Gesellsch 4'7, page 1336) S02.N.K.CH3 4) However the investigations of Gabriel did not extend to the treatment of bodies of the general type (JO-CHzX that is to say to the derivatives of the above mentioned compounds having a mono-hydroxylated nucleus. Now, .in View thereof, it constitutes an important and unexpected progress in this particular art that of these hydroxylated compounds it is possible to obtain bodies of the general composition SOz.CuH4.CHa

CO.CH2.N

of radicals,- while, on the other hand the substitution of only the hydrogen of the hydroxylgroup by other kinds of radicals (alkyls or acyls) produces very satisfactory and sometimes almost theoretical yields. Gabriel states expressly that with his method of working he has never succeeded to obtain a larger yield than 50 percent of the theoretical, In view of this fact the differentiating behavior of the oXy-compounds mentioned according to this invention, was entirely out of the ordinary and could not be expected.

. It should be understood that instead of salts of the.toluol-sulphon-alkyl-amids it is possible to employ other amido-acid-salts.

The hydroxy-w amino-,aceto-phenones with a substitution-group adjacent the nitrogen-atom are obtained'in their turn by the treatment of the compounds mentioned above with reference to the type A by treating the compounds of this type A with mineral acids at an increased tem'- perature, and by this treatment the acyl disposed at the hydroXyl-group is likewise removed. In this manner the N-alkyl-substituted hYdI'OXY-wamino-acetophenones can be obtained in a comparatively easy manner and in pure condition and at a highly satisfactory yield. My present process of obtaining omega-substituted hydroxyl-aminosubstituted acetophenone-bodies or hydroxyphenyl alkyl or aryl amino or acyl-amino ketone bodies is clearly distinguished from my own previous suggestion of acting with monoand with di-alkyl-amines on monohydroxy-a-aminm acetophenone-derivatives by the fact that a much better yield and better products are obtained than in my previous process in which there is the difficulty that a resinous mass is first separated as a result of the formation of pyrazines produced by the action of the free amines of the hydrocarbons. In my present process this difiiculty is overcome by the absence of such free amines and by the use of acid-amides with but one monovalent substituent combined with the nitrogen, the yield being moreover further improved by the use of parent materials in which the hydrogen of the free hydroxyl-group has been substituted or closed by acylor alkylor aryl-substituents.

Example I .-13 grams meta-acet-oxy-bromineacetophenone CO-GHzBr (1) OqH4 are shaken up with 11.2 grams para-toluenesulphone-methylamin-potassium-salt and with liquor is sucked off from the potassium-bromide that has separated out, and the filtrate is about 50 cc. acetone for some hours, the resulting .1

stitutes the desired intermediate product which melts at a temperature between 120 and 121 degrees.

6 grams of this intermediate product are boiled for one hour with 25 cc. of a 55%-aqueous hydroiodic acid, the aqueous solution is freed from the para-toluenesulpho-iodide formed by repeated shaking with ether, and it is then oversaturated with ammonia. This Will-cause the separation of shining leaflets of the meta-hydroxy-methylamino-acetophenone, melting at 135 degrees C. The hydrochloride of this basic, substance, if crystallized from dilute alcohol forms crystals of the melting point 234 degrees C. yield being 66%.

Example II .'72 grams parabenZoyl-hydroxyomega-bromo acetophenone are shaken for one hour with 50 grams para-toluene-sulphonemethyl-amine-potassium-salt and acetone; the resulting separated mass is washed with water and alcohol and the crystalline residue of the acetone-mother-liquor is treated in the same manner. Thus the desired compound is obtained at a yield of 90 percent of the theoretical quantity.Then this compound is treated with fuming hydrochloric acid at 100 degrees C., and the mixture obtained is then operated upon as in the first example, and by this means upon precipitation of the aqueous solution with ammonia the parahydroxymethylamino-acetophenone is obtained which melts at 148 degrees C. The hydrochloride melts at 238-240 Centigrade. Upon analysis the following composition was found 53.37%0, 6.12% H (calculated for C9H12O2N.C1= 53.57% C, 6.00% H).

It is to be understood that the scope of the invention is not intended to be limited beyond the terms of the appended claims or of the requirements of the prior art, and that the invention may find expression in other exemplifications beyond those hereinbefore recited.

I claim:-

1.,As a new product meta-hydroxy-methylamino-acetophenone having the structural formula CO.CH2.NH.CH3 (l) u OH (3 melting at 135 C. and forming glossy leaflets. 2. A sulpho-amido substitution product of omega substituted acetoxy-acetophenone having the structural formula CO.CH2.1|\T.SOI.O6H4.CH3

and melting at a temperature of between 120 and 121 degrees C.

3. A method for making mono-hydroxy-N- alkyl-amino-acetophenones which consists in reacting compounds of the type oocmx 06K! J l 7 oY in which X is an halogen and Y an alkyl or acyl group, with alkali-metal salts of aromatic sulfamides, separating the resulting organic compound from the alkali metal halogenide formed and saponifying said organic compound.

HELMUT LEGERLOTZ.

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